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PULSATILE DRUG DELIVERY SYSTEM: A REVIEW


b) Drug release from intelligent gels responding to antibody concentration.
There are numerous kinds of bioactive compounds which exist in the body. Recently, novel gels were developed which responded to the change in conbecentration of bioactive compounds to alter their swelling/deswelling characteristics. Miyata and co-workers [57-58] focused on the introduction of stimuli-responsive cross-linking structures into hy-drogels. Special attention was given to antigen antibody complex formation as the cross-linking units in the gel, because specific antigen recognition of an antibody can provide the basis for a new device fabrication.

c) Electric stimuli-responsive pulsatile release
The combination of developments in several technologies, such as microelectronics and micromachin ing, as well as the potential need for chronotherapy, have currently assisted the development of electronically assisted drug delivery technologies. These technologies include iontophoresis, infusion pumps, and sonophoresis [59]. Several approaches have also been presented in the literature describing the preparation of electric stimuli-responsive drug delivery systems using hydrogels.
Kishi et al. [60] developed an electric stimuli induced drug release system using the electrically stimulated swelling /deswelling characteristics of polyelectrolyte hydrogels. They utilized a chemomechanical system, which contained a drug model within the polyelectrolyte gel structure. These gels exhibited reversible swelling / shrinking behavior in response to on–off switching of an electric stimulus. Thus, drug molecules within the polyelectrolyte gels might be squeezed out from the electric stimuli-induced gel contraction along with the solvent flow. To realize this mechanism, poly(sodium acrylate) microparticulate gels containing pilocarpine as a model drug were prepared. [61]

4. RECENT ADVANCES IN THE PULSATILE DRUG DELIVERY
 Nowadays pulsatile drug delivery systems are gaining importance in various disease conditions specifically in diabetes where dose is required at different time intervals. Among these systems, multi-particulate systems (e.g. pellets) offer various advantages over single unit which include no risk of dose dumping, flexibility of blending units with different release patterns, as well as short and reproducible gastric residence time [62]. Multiparticulate systems consists pellets of different release profile which can be of any type like time dependent, pH dependent, micro flora activated system as discussed in the previous sections. Site and time specific oral drug delivery have recently been of great interest in pharmaceutical field to achieve improved therapeutic efficacy. Gastroretentive drug delivery system is an approach to prolong gastric residence time, thereby targeting sitespecific drug release in upper gastrointestinal (GI) tract. Floating drug delivery system (FDDS) and bioadhesive drug delivery are widely used techniques for gastro retention. Low density porous multiparticulate systems have been used by researchers for formulation of FDDS. Sharma and Pawar developed multiparticulate floating pulsatile drug delivery system using porous calcium silicate and sodium alginate for time and site specific drug release of meloxicam [63]. Various pulsatile technologies have been developed on the basis of methodologies as discussed previously. These includes OROS® technology, CODAS® technology, CEFORM® technology, DIFFUCAPS® technology, Three-dimensional printing®, timerx® etc.

5. CURRENT SITUATION AND FUTURE SCOPE
Now a day's pulsatile drug delivery is gaining popularity. The prime advantage in this drug delivery is that drug is released when necessity comes. As a result chance of development of drug resistance which is seen in conventional and sustained release formulations can be reduced. Furthermore, some anticancer drugs are very toxic. These drugs give hazardous problems in conventional and sustained release therapies. Now many FDA approved chronotherapeutic drugs are available in the market. This therapy is mainly applicable where sustained action is not required and drugs are toxic. Key point of development of this formulation is to find out circadian rhythm i.e. suitable indicator which will trigger the release of drug from the device. Another point is absence of suitable rhythmic biomaterial which should be biodegradable, biocompatible and reversibly responsive to specific biomarkers in rhythmic manner. Regulatory is another big question. In preapproval phase it is sometimes difficult to show chronotherapeutic advantage in clinical settings. In postapproval phase causal recreational drug abuse along with on a much larger scale, by the criminal diversion of these modified formulations for profit have arisen problems. The FDA has now heavily relied on the development and implementation of risk management programs as a strategy to allow an approval of a drug to go forward while exercising some restrictions. Many researches are going on the pulsatile drug delivery to discover circadian rhythm with suitable device in the world. In future this delivery will be a leading way to deliver therapeutic agents due to its some unique characters like low chance of dose dumping, patient compliance and the above factors. [64]

6. ADVANTAGES OF PULSATILE DRUG DELIVERY SYSTEM: [65,66]
1. Extended daytime or nighttime activity
2. Reduced side effects
3. Reduced dosage frequency
4. Reduction in dose size
5. Improved patient compliance
6. Lower daily cost to patient due to fewer dosage units are required by the patient in therapy.
7. Drug adapts to suit circadian rhythms of body functions or diseases.
8. Drug targeting to specific site like colon.
9. Protection of mucosa from irritating drugs.
10. Drug loss is prevented by extensive first pass metabolism .
11. Patient comfort and compliance: Oral drug delivery is the most common and convenient for patients, and a reduction in dosing frequency enhances compliance.

7. LIMITATIONS OF PULSATILE DRUG DELIVERY SYSTEM: [66]
Pulsatile drug deleivery system have certain limitation, so in many cases these drug delivery system is fails,
• Multiple manufacturing steps in case of Multiparticulate pulsatile drug delivery system.
• Low drug load
• Incomplete release
• In-vivo variability in single unit pulsatile drug delivery system.

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palak motan
Offline
Joined: 2010-06-06
re pulsatile delivery of antibiotic

sir, your article was very informative . sir. i am a M.pharm student and want todo project pulsatile delivery of antibiotic for travelers diarrohea since the dose of drug is 200mg 3 times a day. is my rationale of msking a pulsatile of antibiotic correct ? Please do reply

maheshrag (not verified)
Pulsatile drug delivery

Mr. Palak motan.......for the diseases which follow circadian rhythms, pulsatile drug delivery is useful.......so in the case of TD there is no need of PDDs. and

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